Exelon(R) Granted EU Marketing Authorization As First Treatment For Dementia Associated With Parkinson’s Disease By European Commission

Novartis announced today that Exelon(R)
(rivastigmine tartrate) has been granted European marketing authorization
by the European Commission for the symptomatic treatment of mild to
moderately severe dementia in patients with idiopathic Parkinson’s disease
(PD) in all 25 European member states.

This makes Exelon, currently indicated for Alzheimer’s dementia, the first
medication available to treat dementia in Parkinson’s patients in the
European Union and the only cholinesterase inhibitor to be authorized for
more than one type of dementia. Exelon has already received marketing
authorization for dementia associated with PD in Switzerland and several
Latin American countries, including Brazil.

The EU approval is based on the results of the EXPRESS study, a
large-scale, randomized, well-controlled study involving 541 patients from
12 study centers in Europe and Canada and follows the positive opinion
granted by the Committee for Medicinal Products for Human Use (CHMP)
earlier this year.

“Exelon provides an important advance in the therapy of dementia associated
with Parkinson’s disease”, said Professor Werner Poewe, Head of Neurology,
University Hospital, Innsbruck, Austria. “In the EXPRESS study, patients
taking Exelon showed significant benefits regarding memory, concentration
and behavioral problems. Patients and their caregivers reported in
particular an increased interest and ability to conduct social
conversations. This does not only translate into a better quality of life
for PD patients suffering from dementia but also a substantial improvement
in the quality of life for their families,” Werner Poewe concluded.

At any one time, up to 40 percent of people with Parkinson’s disease suffer
from dementia . Patients with dementia associated with Parkinson’s disease
typically have problems with memory, concentration, activities of daily
living, as well as depression, anxiety, apathy and hallucinations .
However, probably due to the absence of treatment, current diagnosis rates
are low.

“When my husband developed dementia associated with Parkinson’s disease, I
became a nervous wreck. He would ask me the same question again and again
and again,” said
Mrs I., spouse of PD patient suffering from dementia. “Since he has started
taking this new medicine he pays more attention, we have conversations and
he can go to the shop by himself. It is wonderful. I know it won’t go away
completely, but these tablets have really changed our lives. Everything is
different now.”

About the EXPRESS study

The regulatory submissions were based on the EXPRESS study (EXelon in
PaRkinson’s disEaSe dementia Study), published in December 2004 in the New
England Journal of Medicine . EXPRESS is the first large-scale clinical
study assessing the efficacy and safety of any treatment in Parkinson’s
disease patients with dementia. Patients taking Exelon showed statistically
significant benefits on a range of symptoms, such as maintaining or
improving memory, concentration and behavioral problems. They were also
able to cope better with everyday activities like watching TV or talking
about current events.

The side effects associated with Exelon during this study were mild to
moderate in nature and included nausea and vomiting. Importantly, motor
scale assessments showed that Parkinsonian symptoms were not worsened
overall relative to baseline or placebo. Mild to moderate tremor was
reported in 10% of Exelon-treated patients, but this resulted in relatively
few withdrawals from the study.

About Exelon

Since 1997, Exelon has been widely used to treat mild to moderately severe
Alzheimer’s dementia in over 70 countries. It belongs to a class of drugs
known as cholinesterase inhibitors (ChEI’s) which increase the activity of
the neurotransmitter acetylcholine in the brain.

Among the ChEI’s, Exelon is the only treatment that inhibits both enzymes
involved in the breakdown of this neurotransmitter – acetylcholinesterase
(AChE) and butyrylcholinesterase (BuChE). This may offer additional
benefits over treatments which inhibit AChE alone. Exelon can maintain both
memory and thinking, help with behavioral problems and affect how patients
cope with the activities of daily living. It may help them communicate
better, interact socially, participate in hobbies and in activities of
daily living.

About Parkinson’s Disease Dementia

Parkinson’s disease is a chronic and progressive neurological condition
estimated to affect 6.3 million people worldwide . Dementia is thought to
occur in up to 40 percent of patients diagnosed with this disease and may
affect up to 80 percent of Parkinson’s patients in advanced age and severe
diseaseError! Bookmark not defined.1, . Parkinson’s patients have a
six-fold increase in the risk of developing dementia compared with elderly
people without Parkinson’s disease.

Like Alzheimer’s, dementia associated with Parkinson’s disease is thought
to result partly from a cholinergic deficit, which causes decreased
transmission of signals between nerves in the brain, especially those that
rely on the neurotransmitter acetylcholine.

Dementia associated with Parkinson’s disease differs clinically from
Alzheimer dementia. Patients with dementia associated with Parkinson’s
disease generally suffer from an impairment of executive function like the
ability to plan or organize and goal-directed behavior. Furthermore they
have more severe visuospatial deficits, apathy, severe attentional deficits
with fluctuations and frequent visual hallucinations.

This release contains certain forward-looking statements relating to the
Company’s business, which can be identified by the use of forward-looking
terminology such as “may offer”, “may help”, “goal is”, or similar
expressions, or by express or implied discussions regarding potential new
indications for Exelon, or regarding potential future revenue from Exelon.
Such forward-looking statements involve known and unknown risks,
uncertainties and other factors that may cause actual results with Exelon
to be materially different from any future results, performance or
achievements expressed or implied by such statements. There can be no
guarantee that Exelon will be approved for any additional indications in
any market or regarding potential future revenue from Exelon. In
particular, management’s expectations regarding commercialization of Exelon
could be affected by, among other things, additional analysis of Exelon
clinical data; new clinical data; unexpected clinical trial results;
unexpected regulatory actions or delays in government regulation generally;
the company’s ability to obtain or maintain patent or other proprietary
intellectual property protection; competition in general; government,
industry, and general public pricing pressures; as well as factors
discussed in the Company’s Form 20-F filed with the US Securities and
Exchange Commission. Should one or more of these risks or uncertainties
materialize, or should underlying assumptions prove incorrect, actual
results may vary materially from those described herein as anticipated,
believed, estimated or expected. Novartis is providing the information in
this press release as of this date and does not undertake any obligation to
update any forward-looking statements contained in this press release as a
result of new information, future events or otherwise.

About Novartis

Novartis has been a leader in the neuroscience area for more than 50 years,
having pioneered early breakthrough treatments for Alzheimer’s disease,
Parkinson’s disease, attention deficit/hyperactivity disorder, epilepsy,
schizophrenia and migraine. Novartis continues to be active in the research
and development of new compounds, is committed to addressing unmet medical
needs and to supporting patients and their families affected by these

Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect
health, treat disease and improve well-being. Our goal is to discover,
develop and successfully market innovative products to treat patients, ease
suffering and enhance the quality of life. Novartis is the only company
with leadership positions in both patented and generic pharmaceuticals. We
are strengthening our medicine-based portfolio, which is focused on
strategic growth platforms in innovation-driven pharmaceuticals,
high-quality and low-cost generics and leading self-medication OTC brands.
In 2005, the Group’s businesses achieved net sales of USD 32.2 billion and
net income of USD 6.1 billion. Approximately USD 4.8 billion was invested
in R&D. Headquartered in Basel, Switzerland, Novartis Group companies
employ approximately 91,000 people and operate in over 140 countries around
the world. For more information, please visit novartis.


1) Cummings JL. Intellectual impairment in Parkinson’s disease: clinical,
pathological and biochemical correlates. J Geriatr Psychiatry Neurol

2) Huber SJ, Paulson GW, Shuttleworth EC. Relationship of motor symptoms,
intellectual impairment, and depression in Parkinson’s disease. J Neurol
Neurosurg Psychiatry 1988;51:855-858.

3) Emre M et al. Rivastigmine for the dementia associated with Parkinson’s
Disease. N Engl J Med 2004;351:29-38.

4) Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the
efficacy and safety of ENA713 (rivastigmine tartrate), a new
acetylcholinesterase inhibitor, in patients with mild to moderately severe
Alzheimer’s disease. Int J Geriatr Psychopharmacol 1998;1:55-65.

5) Rosler M, Anand R, Cicin-Sain A et al. Efficacy and safety of
rivastigmine in patients with Alzheimer’s disease: international randomized
controlled trial. Br Med J 1999;318:633-40.

6) Global Declaration on Parkinson’s Disease launched by the Working Group
on PD at the 7th World PD International Symposium, 7th December 2003 in
Mumbai, India. epda.eu/globaldeclaration-about.shtm.

7) McKeith IG and Mosimann UP. ‘Dementia with Lewy bodies and Parkinson’s
disease.’ Parkinsonism & Related Disorders 10 (2004) S15-S18.

8) Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sorensen
P.Risk of dementia in Parkinson’s disease: a community-based, prospective
study. Neurology. 2001;56(6):730-6.


View drug information on Exelon.

Failed Vaccine Mystery Solved By Hopkins-Led Team

Research led by Johns Hopkins Children’s Center scientists has figured out why a respiratory syncytial virus vaccine used in 1966 to inoculate children against the infection instead caused severe respiratory disease and effectively stopped efforts to make a better one. The findings, published online on Dec. 14 in Nature Medicine, could restart work on effective killed-virus vaccines not only for RSV but other respiratory viruses, researchers say. The new findings also debunk a popular theory that the 1966 vaccine was ineffective because the formalin used to inactivate the virus disrupted critical antigens, the substances that stimulate the production of protective antibodies.

Instead, researchers said, the problem occurred when the antibodies created by the vaccine failed to successfully bind to the real virus after exposure to it, thereby incapacitating it. Like vaccines against influenza and polio, the 1966 formalin-inactivated RSV vaccine produced antibodies, but these turned out to be defective ones with poor virus-binding ability.

“We have found the root cause of the problem, and in doing so we have uncovered clues that will help us design even safer and more effective vaccines in the future,” says senior investigator Fernando Polack, M.D., an infectious disease specialist at Hopkins Children’s.

More specifically, in a series of experiments, the research team discovered that the old RSV vaccine failed to trigger a “signaling” mechanism – called toll-like receptor activation – that helps the immune system recognize a virus and mount a defense against it. Toll-like receptor activation is the first in cascade of immune system responses that occur after infection, firing off signals to other immune cells telling them to produce and release antibodies.

First, the team compared immune system response in three groups of mice: those vaccinated with a placebo, those with a weakened form of the RSV virus, and those with inactivated or killed-virus vaccines. Researchers found that in the last group, the toll-like receptor activation was weak and led to the production of defective antibodies.

Next, they infused the vaccine with a substance that stimulates toll-like receptor activation to see if it would created antibodies better equipped to bind to and neutralize the virus. Indeed, mice vaccinated with the toll-like receptor stimulating form of the inactivated vaccine produced antibodies with better binding and virus-neutralizing ability. Mice immunized with this form of the vaccine had milder symptoms and less inflammation in the bronchi and the lungs when infected with the real RSV.

RSV is the most common culprit of serious viral infections in newborns and infants younger than1 year, and the leading cause of hospitalization in this age group. Half of all infants contract RSV during their first year of life, and hospitalizations for children with RSV have more than doubled in recent decades, researchers say. To date, there is no vaccine against RSV.

Other investigators in the study: Guillermina Melendi and Johanna Zea Hernandez of Johns Hopkins; Herng-Yu Chang and Wayne Mitzner, of the Johns Hopkins Bloomberg School of Public Health; Maria Florencia Delgado, Silvina Coviello, A. Clara Monsalvo, Juan Batalle, Leandro Diaz of the INFANT Foundation, Buenos Aires, Argentina; Alfonsina Trento and Jose Melero, of Instituto de Salud Carlos III, Madrid, Spain; Jeffrey Ravetch, of Rockefeller University, New York; Pablo Irusta of Georgetown University School of Medicine. The research was funded by an NIH grant and money from the Thomas and Carol McCann Innovative Research Fund for Asthma and Respiratory Diseases.

Source: Ekaterina Pesheva

Johns Hopkins Medical Institutions

Motavizumab Cuts RSV Burden In High-Risk Infants

The investigational second-generation humanized monoclonal antibody motavizumab significantly decreases hospitalizations due to respiratory syncytial virus (RSV) and outpatient acute lower respiratory tract infections (ALRIs) in term American Indian infants at high risk of RSV disease, according to interim results of an ongoing phase III study released at the annual meeting of the Pediatric Academic Societies (PAS).

The trial is the first to assess the use of an RSV antibody to prevent serious RSV disease in healthy American Indian infants thought to be at high risk for serious RSV disease.

Kate O’Brien, MD, at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, along with the American Indian RSV Prevention Study Team,
randomized 1,410 term, healthy American Indian infants in a 2:1 design to received five monthly intramuscular (IM) doses of motavizumab, 15 mg/kg, or placebo during their first RSV season.

“Respiratory syncytial virus is a leading cause of ALRIs, including hospitalization in infants,” Dr. O’Brien, associate professor of medicine, said. “Otherwise healthy, full-term Navajo, White Mountain Apache and Alaska Native infants have rates of RSV hospitalization that are over three times higher than those of similarly aged children in the general U.S. population and on a par with those among children with underlying conditions.”

Study participants were healthy, full-term children who were six months of age or younger at the time of randomization.

The primary endpoint was RSV hospitalizations through day 150.

In an interim intent-to-treat analysis, motavizumab-treated patients had an 83 percent reduction in the incidence of RSV hospitalizations compared to placebo-treated patients (8.3 percent for placebo versus 1.4 percent for motavizumab; p

PureGreen24 Meets CDC’s Recommendation For Infection Control For Care Of Patients With Swine Influenza A (H1N1) Virus In Home And Healthcare Settings

Pure Green, LLC, distributors of PureGreen24, confirmed that PureGreen24, powered by PURE Bioscience’s (NASDAQ: PURE) patented silver dihydrogen citrate (SDC) antimicrobial, meets the recommendations by the United States Centers for Disease Control (CDC) for infection control for care of patients with confirmed or suspected Swine Influenza A (H1N1) virus in both home and healthcare settings.

According to the CDC, human transmission of flu occurs through coughing or sneezing of people infected with the influenza virus. People may become infected by touching something with viruses on it and then touching their mouths or noses.

Guidance published by the CDC on April 24, 2009 for infection control in healthcare settings advises: “disinfection strategies used during influenza seasons can be applied to the environmental management of swine influenza.” Additional guidance published on April 25, 2009 for infection control in the home recommends keeping “surfaces (especially bedside tables, surfaces in the bathroom, and toys for children) clean by wiping them down with a household disinfectant according to directions on the product label.”

Pure Green’s disinfectant has been registered by the EPA specifically for use on toys, cribs, high chairs and other sensitive areas of the home as well as for use in multitudes of environments, including hospitals, schools and offices.

David Stetson, Co-Founder of Pure Green, LLC, stated, “PureGreen24 is effective against Influenza A. Should the current outbreak become pandemic, Pure Green has the capacity to react to the needs of federal and state governments, healthcare institutions, schools and consumers in the U.S. and Puerto Rico seeking to effectively stem the spread of swine flu.”

Pure Green, LLCFurther information on Swine Flu

See a Map Of H1N1 Outbreaks
See our Mexico Swine Flu Blog

Gene Key To Alzheimer’s-Like Reversal In Mice Identified By MIT-Led Team

A team led by researchers at MIT’s Picower Institute for Learning and Memory has now pinpointed the exact gene responsible for a 2007 breakthrough in which mice with symptoms of Alzheimer’s disease regained long-term memories and the ability to learn.

In the latest development, reported in the May 7 issue of Nature, Li-Huei Tsai, Picower Professor of Neuroscience, and colleagues found that drugs that work on the gene HDAC2 reverse the effects of Alzheimer’s and boost cognitive function in mice.

“This gene and its protein are promising targets for treating memory impairment,” Tsai said. “HDAC2 regulates the expression of a plethora of genes implicated in plasticity – the brain’s ability to change in response to experience – and memory formation.

“It brings about long-lasting changes in how other genes are expressed, which is probably necessary to increase numbers of synapses and restructure neural circuits, thereby enhancing memory,” she said.

The researchers treated mice with Alzheimer’s-like symptoms using histone deacetylase (HDAC) inhibitors. HDACs are a family of 11 enzymes that seem to act as master regulators of gene expression. Drugs that inhibit HDACs are in experimental stages and are not available by prescription for use for Alzheimer’s.

“Harnessing the therapeutic potential of HDAC inhibitors requires knowledge of the specific HDAC family member or members linked to cognitive enhancement,” Tsai said. “We have now identified HDAC2 as the most likely target of the HDAC inhibitors that facilitate synaptic plasticity and memory formation.

“This will help elucidate the mechanisms by which chromatin remodeling regulates memory,” she said. It also will shed light on the role of epigenetic regulation, through which gene expression is indirectly influenced, in physiological and pathological conditions in the central nervous system.

“Furthermore, this finding will lead to the development of more selective HDAC inhibitors for memory enhancement,” she said. “This is exciting because more potent and safe drugs can be developed to treat Alzheimer’s and other cognition diseases by targeting this HDAC specifically,” said Tsai, who is also a Howard Hughes Medical Institute investigator. Several HDAC inhibitors are currently in clinical trials as novel anticancer agents and may enter the pipeline for other diseases in the coming two to four years. Researchers have had promising results with HDAC inhibitors in mouse models of Huntington’s disease.

Remodeling structures

Proteins called histones act as spools around which DNA winds, forming a structure in the cell nucleus known as chromatin. Histones are modified in various ways, including through a process called acetylation, which in turn modifies chromatin shape and structure. (Inhibiting deacetylation with HDAC inhibitors leads to increased acetylation.)

Certain HDAC inhibitors open up chromatin. This allows transcription and expression of genes in what had been a too tightly packaged chromatin structure in which certain genes do not get transcribed.

There has been exponential growth in HDAC research over the past decade. HDAC inhibitors are currently being tested in preclinical studies to treat Huntington’s disease. Some HDAC inhibitors are on the market to treat certain forms of cancer. They may help chemotherapy drugs better reach their targets by opening up chromatin and exposing DNA. “To our knowledge, HDAC inhibitors have not been used to treat Alzheimer’s disease or dementia,” Tsai said. “But now that we know that inhibiting HDAC2 has the potential to boost synaptic plasticity, synapse formation and memory formation, in the next step, we will develop new HDAC2-selective inhibitors and test their function for human diseases associated with memory impairment to treat neurodegenerative diseases.”

The researchers conducted learning and memory tasks using transgenic mice that were induced to lose a significant number of brain cells. Following Alzheimer’s-like brain atrophy, the mice acted as though they did not remember tasks they had previously learned.

But after taking HDAC inhibitors, the mice regained their long-term memories and ability to learn new tasks. In addition, mice genetically engineered to produce no HDAC2 at all exhibited enhanced memory formation.

The fact that long-term memories can be recovered by elevated histone acetylation supports the idea that apparent memory “loss” is really a reflection of inaccessible memories, Tsai said. “These findings are in line with a phenomenon known as ‘fluctuating memories,’ in which demented patients experience temporary periods of apparent clarity,” she said.

In addition to Tsai, co-authors are Picower postdoctoral associate Ji-Song Guan; and colleagues from Massachusetts General Hospital; Harvard Medical School; the Whitehead Institute for Biomedical Research; MIT’s Department of Biology; the Dana Farber Cancer Institute; and the Netherlands Cancer Institute.

This work is supported by the National Institute for Neurological Disorders and Stroke, the Stanley Center for Psychiatric research at the Broad Institute of Harvard and MIT; the NARSAD, a mental health foundation, the National Cancer Institute, the Damon-Runyon Cancer Research Foundation; the Dutch Cancer Society; the National Institutes of Health; and the Robert A. and Renee E. Belfer Institute for Applied Cancer Science.

Deborah Halber, Picower Institute

Elizabeth Thomson

Massachusetts Institute of Technology

FDA Agrees To Review Cimzia(R) File For The Treatment Of Rheumatoid Arthritis

UCB announced that the U.S. Food
and Drug Administration (FDA) agreed to accept, for filing and review, a
biologics license application (BLA) for Cimzia(R) (certolizumab pegol) for
the treatment of adult patients with active rheumatoid arthritis (RA).
Cimzia(R) is an investigational agent. If approved, Cimzia(R) will be the
first and only PEGylated anti-TNF (Tumor Necrosis Factor) biologic therapy
available for the treatment of rheumatoid arthritis.

“As a new anti-TNF, we believe that Cimzia(R) would provide an
important new option for people living with this disease,” said Olav
Hellebo, President Inflammation Operations, UCB.

The BLA is based on data from more than 2,367 patients and includes
three multi-center, placebo-controlled Phase III trials which were recently
presented at the American College of Rheumatology (ACR) Annual Scientific

In these studies, Cimzia(R), given with methotrexate, was shown to be
significantly more effective than methotrexate alone for the inhibition of
joint damage progression in patients with active RA as early as 24 weeks
(RAPID 1 and RAPID 2). Cimzia(R) was shown to rapidly reduce the signs and
symptoms of active RA with peak ACR50 and 70 responses achieved at 14 and
16 weeks. Improvement in physical function and quality of life measures
were also seen for up to one year (RAPID 1). Further, Cimzia(R)
administered as monotherapy showed significant improvement in signs and
symptoms of RA from week 1, and this benefit was maintained through week 24
(Study 011). The most commonly occurring adverse reactions were headache,
nasopharyngitis, and upper respiratory tract infections. Reported serious
adverse reactions were infections (including tuberculosis) and malignancies
(including lymphoma), consistent with findings from other trials in the
anti-TNF class.

Preparation for submission of a Marketing Authorization Application
(MAA) to the European Medicines Agency (EMEA) for Cimzia(R) in the
treatment of RA is ongoing, with filing planned in the first half of 2008.

In September 2007, Cimzia(R) was approved in Switzerland for the
treatment of Crohn’s disease and it was launched in January 2008.

About Rheumatoid Arthritis

RA is a progressive autoimmune disease that causes chronic inflammation
of the joints. It is estimated that five million people suffer from RA
globally, with 0.3 percent to 1 percent of the population in industrialized
countries suffering from the disease. Women are three times more likely to
be affected than men. Although it can affect people of all ages, the onset
of RA usually occurs between the ages of 35-55.

Traditional treatments for RA include nonsteroidal anti-inflammatory
drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs
(DMARDs), with biological therapies a more recent addition.

About UCB

UCB, Brussels, Belgium (ucb-group) is a global leader in the
biopharmaceutical industry dedicated to the research, development and
commercialization of innovative pharmaceutical and biotechnology products
in the fields of central nervous system disorders, allergy/respiratory
diseases, immune and inflammatory disorders and oncology. UCB focuses on
securing a leading position in severe disease categories. Employing around
12,000 people in over 40 countries, UCB achieved revenue of 3.5 billion
euro in 2006 on a pro forma basis. UCB S.A. is listed on Euronext Brussels.

UCB Forward-Looking Statement

This news release contains forward-looking statements that involve
risks and uncertainties, including statements with respect to the
development and commercialization of certolizumab pegol. Among the factors
that could cause actual results to differ materially from those indicated
by such forward- looking statements are: the results of research,
development and clinical trials; the timing and success of submission,
acceptance, and approval of regulatory filings; the time and resources UCB
devotes to the development and commercialization of certolizumab pegol and
the scope of UCB’s patents and the patents of others.


Why Better TB Care In Africa Is In European Interests

The recent outbreak of a lethal combination of HIV and TB in southern Africa has prompted Britain to pledge an extra US$ 3.15 million (??1.6 million) to the World Health Organization’s Stop TB partnership. The fact that all G8 countries admit the presence of TB strains that are extremely resistant to drugs (so-called Extensively Drug-Resistant TB or XDR-TB) brings home the WHO’s unsettling message for World TB Day – ‘TB anywhere is TB everywhere’.

The slogan is backed by sobering statistics. More than 365 000 cases of TB were reported in the Europe in 2005, 10,000 more than for 2004. The figures for Europe are worrying enough, but XDR-TB in southern Africa is particularly threatening given the prevalence there of HIV infection. Although TB can infect anyone, people with HIV are at greater risk because they are less able to fight off infection. If, as is so often the case, they have undiagnosed TB, they will provide good conditions for the development of XDR-TB.

“Supporting patients to complete a full course of TB drugs is the key to preventing drug resistance developing”. says John Walley, Professor in International Public Health and co-director of the DFID funded Communicable Disease Research Programme (COMDIS) based in Leeds.

XDR-TB develops when people infected with TB already resistant to first-line treatments fail to complete courses of second-line drug treatment. The WHO wants US$ 650 million per year for the next eight years to diagnose and treat more than 1.5 million people with drug-resistant TB but the success of its TB strategy relies on high levels of compliance of TB patients in taking daily medication over 6-8 months. A tall order when you consider how difficult it is to complete even a one-week course of antibiotics.

In this light Britain’s response to the call for more funds may seem like a drop in the ocean but it is additional to long-term support of research such as COMDIS, which focuses on delivering better TB care in poorer countries. Such research has already helped the WHO to refine its TB strategy.

Professors John Walley and James Newell and their colleagues in Pakistan and Nepal have been researching ways of improving TB treatment within national TB programmes for many years. Their work, and research by other scientists in other countries, helped the WHO to move away from rigid directly observed treatment to stressing patient-friendly support.

Rather than requiring people to make expensive visits to clinics in order to be supervised while they take their TB medication, the emphasis is now on supporting the patients’ families and communities in helping people with TB through their illness and long-term treatment.

The COMDIS model embeds research within national TB programmes and has
proved hugely successful in Pakistan where new guidelines for TB health workers have been taken up nationwide. ‘We have contributed to a rise in recorded successful treatment rates from around 30 percent before the national scale-up of training to an average of 84 percent since’, says Professor Walley.

COMDIS has taken the patient-friendly approach to TB care to Swaziland and has begun to apply this to anti-retroviral treatment for people with HIV. Community-based care is part of the package to improve adherence to treatment and avoid the development of resistance to TB and anti-retroviral drugs. ‘TB does not respect international borders’, Professor Walley points out. ‘Controlling TB in these countries reduces the risk to us in the UK’.

Department for International Development (DFDI)

Pittsburgh Researchers First To Profile Gene Activity In Acutely Ill Idiopathic Pulmonary Fibrosis Patients

The first findings from a one-of-a-kind, patient-driven effort to provide lung tissue for research might help doctors predict when patients with idiopathic pulmonary fibrosis (IPF) are becoming dangerously ill and also could point the way to interventions that could sustain them until life-saving transplants can be performed.

According to senior author Naftali Kaminski, M.D., associate professor of medicine, computational biology and pathology, and director of the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases at the University of Pittsburgh School of Medicine and UPMC, the research published today in the American Journal of Respiratory and Critical Care Medicine addresses a dilemma in IPF care that currently is unsolved.

“Approximately 10 percent of patients develop an acute phase that in most cases is lethal,” Dr. Kaminski explained. “There has been very little understanding of the molecular basis of this syndrome, but because of the dedication of our patients and their families, we are getting closer to some answers.”

For most patients, the lung-scarring disease progresses gradually and lung function slowly deteriorates. But there is neither a cure nor effective treatment, so median survival is about three years. For unknown reasons, some IPF patients experience rapid declines that cause diffuse damage of the lung alveoli, the tiny sacs where the exchange of oxygen and carbon dioxide occurs.

To better understand the molecular mechanisms of disease exacerbation or, as Dr. Kaminski puts it, acceleration, the researchers compared the gene activity profile of the lungs of eight IPF patients whose disease was dramatically worsening when they died with those of 23 stable IPF patients and 15 people with healthy lungs.

In the first analysis of its kind, “gene activity patterns were found to be more similar among all IPF patients compared to healthy people,” said lead author Kazuhisa Konishi, M.D., a visiting postdoctoral fellow in Dr. Kaminski’s lab who performed the gene profiling. “But nearly 600 genes were differentially expressed between IPF patients who had accelerated disease and those who were stable.”

There was no evidence that infection or inflammation was the cause of disease acceleration, he noted. Instead, there were indications that the cells of the alveolar epithelium, which is the tissue that covers the surface of the air sacs, were rapidly dying.

“That could mean that drugs that are used to protect the epithelium in other illnesses, such as cancer, might help IPF patients survive an exacerbation,” said study co-author Kevin Gibson, M.D., associate professor in the Division of Pulmonary, Allergy and Critical Care Medicine at Pitt School of Medicine and medical director of the Simmons Center. “If we can keep them alive, there’s a chance they could get a life-saving lung transplant.”

To test whether the changes in the lungs could be revealed in the blood, the Pitt investigators contacted Dr. Kaminski’s longtime collaborator, Dong Soon Kim, M.D., a renowned IPF researcher at Asan Medical Center and the University of Ulsan in Seoul, South Korea, who has been at the forefront of studying the acceleration syndrome. With her help, they found that levels of a protein called alpha-defensin were particularly high in the blood of patients experiencing an exacerbation. If the findings are verified with more research, which is underway, the proteins could be the first biomarker blood tests that doctors could track to identify patients at risk for sudden deterioration of lung function.

“This work opens an important window into the mystery of why patients with lung fibrosis suddenly decompensate and how to identify these patients for more aggressive therapies,” said Mark T. Gladwin, M.D., chief of Pitt’s Division of Pulmonary, Allergy and Critical Care Medicine. “Our current research efforts in the division focus on the development of novel therapeutics that will target the molecular pathways identified by our basic science laboratories.”

If not for the altruism of IPF patients, the research and its promising results would not have been possible, Dr. Kaminski noted. The IPF tissue samples used for the study were collected through the Simmons Center’s warm autopsy program, which is the only one for lungs in the world.

Several years ago, an IPF patient told Kathleen Lindell, Ph.D, R.N., the Simmons Center nurse, a quality of life researcher and a study co-author, that he wanted to aid research efforts by donating his lungs to science after death. In response, she developed the warm autopsy program.

“The tissue has to be collected within six hours of death, so it demands a great deal of flexibility and commitment on the part of caregivers and family,” Dr. Lindell said. “The gene components of the lung cells degrade very quickly, so without the warm autopsy protocol, we couldn’t have done the activity profiling that was the foundation of this research.”

Other study authors include Thomas J. Richards, Ph.D., Yingze Zhang, Ph.D., Simmons Center; Rajiv Dhir, M.D., Michelle Bisceglia, and Samuel A. Yousem, M.D., Department of Pathology; Sebastien Gilbert, M.D., Department of Thoracic Surgery, all from the Pitt School of Medicine; and Jing Woo Song, Asan Medical Center, University of Ulsan, Seoul, South Korea.

The research was funded by the National Institutes of Health and by the Dorothy P. and Richard P. Simmons Endowed Chair for Interstitial Lung Diseases.

University of Pittsburgh School of Medicine

Discovery Of New Drug Target For Inflammatory Disease By UC Davis Researchers

UC Davis researchers have defined a cellular process that promotes inflammation and, at the same time, found an important starting point for identifying and testing new drugs for diseases such as sepsis, rheumatoid arthritis, cardiovascular disease and some cancers.

The scientists discovered that a protein called sPLA2-IIA binds to two integrins labeled alpha-V-beta-3 and alpha-4-beta-1, causing them to rapidly multiply and boosting an immune system response already gone awry due to disease.

“We have known for a while that this protein is elevated with inflammation,” said Yoshikazu Takada, UC Davis professor of dermatology and lead author of the study, which appears in The Journal of Biological Chemistry. “Our outcome shows with much more precision how the protein actually works to advance inflammation. The potential impact of the finding on our ability to block inflammation and stop the disease process in its tracks is enormous.”

Protein sPLA2-IIA has been a major drug discovery target for years, but efforts to counteract the protein have yielded mixed results. Takada explains that this is due to the fact that its intercellular relationships in humans were not well-known. Scientists have previously identified receptors for the protein in mice cells. However, Takada and his team are the first to find that the protein binds to completely different receptors – the two integrins – in human cells.

Integrins are the “networkers” of the immune system, playing key roles in the attachment of cells to other cells. Integrins are also important to signal transduction, the process by which a cell transforms from one kind of signal or stimulus into another.

“We need to know the mechanisms of inflammation to be able to disrupt it,” said Takada. “Now that we know more about how this protein interacts with these integrins, researchers can be much more successful in screening potential drugs that can block the binding process and hopefully the immune response it kicks into overdrive as well.”

In the current study, Takada and team evaluated the possibility of integrin binding by sPLA2-IIA using a computer program that predicts how small molecules bind to receptors. They then performed laboratory experiments using human cells to confirm the resulting predictions.

The researchers conducted additional experiments using human leukemia and lymphoma cell lines, because they are known to express integrins, in order to measure changes in the inflammatory response due to sPLA2-IIA-integrin binding. They found an increase in the number of monocytes, which are important first-line defenders for the immune system responsible for attacking foreign substances in the body. At elevated levels, monocytes indicate an overresponsive immune system.

The involvement of integrins to the inflammatory process is of particular interest to study co-author Kit Lam, chief of hematology and oncology with UC Davis Cancer Center.

“These two and other integrins are found on cancer cells,” Lam explained. “And inflammation certainly plays a role in the onset, progression and maintenance of certain cancers. This outcome could have a huge impact on our work in finding medications that halt or at least reduce the impact of inflammation on this disease.”

Takada and his colleagues will next be working to screen for molecules that block the binding of sPLA2-IIA to integrins and show that this blockage is enough to shut down an unwanted inflammatory response.

“We cannot ignore integrins anymore,” Takada said. “More basic research is needed to understand how integrin-binding results in pro-inflammatory signals. We have to continue to better understand the integrin signaling process if we are to find more potential drug targets for the treatment of inflammation.”

In addition to Takada and Lam, additional UC Davis study authors were Chun-Yi Wu, graduate student, Department of Hematology and Oncology; and – all from the Department of Dermatology – Jun Saegusa, postdoctoral fellow; Nobuaki Akakura, postdoctoral fellow; Case Hoogland, research assistant; Zi Ma, postdoctoral fellow; Fu-Tong Liu, professor and chair; and Yoko Takada, staff research associate. This research was supported by grants from the American Heart Association and the National Institutes of Health.

Research from the UC Davis Department of Dermatology makes important overall contributions to science and medicine, including allergic inflammation, skin cancer, wound repair, autoimmunity, and cell growth factors and inhibitors. For more information, visit the UC Davis Department of Dermatology.

Source: Karen Finney

University of California – Davis – Health System

WHO $ 1.3 million appeal to help meet Niger’s health needs

A locust infestation in 2004 coupled with drought the same year and in 2005 has caused a severe food crisis in Niger. Based on a joint assessment conducted in March of this year, the Government, United Nations agencies and partner NGOs estimate that 3.6 million people have been affected. Approximately 2.5 million people are extremely vulnerable and require food assistance. An estimated 160 000 children in Niger are moderately malnourished and an additional 32 000 children are severely malnourished.

Malnutrition coupled with lack of safe water and poor sanitation (41% of the population does not have sustainable access to an improved water source) increases the risk of outbreaks of communicable diseases. It is estimated that more than 50% of the population does not have access to primary health care. If allowed to continue unchecked, this crisis could result in many deaths from associated illnesses such as cholera, respiratory diseases, diarrhoea, and malaria.

A cholera outbreak has already affected 61 people and killed ten in the district of Bouza in Tahoua region. As part of the health response, WHO will ship eight cholera kits to Niger this week in preparation to manage up to 800 severe cases of cholera.

Following a recent assessment mission in Niger between 27 July and 2 August, the initial World Health Organization (WHO) Flash Appeal has been revised from US$ 400 000 to US$ 1.3 million. This money is urgently needed for four projects to be implemented during the next six months: disease and nutrition surveillance and outbreak response, nutritional case management (building capacities to treat malnutrition at health centre level), supporting development of health policy to improve access to essential health care services by increasing reliability and affordability, and strengthening health sector coordination and information management.

Says mission leader, Emilienne Anikpo, “The assessment we conducted was crucial in allowing us to better understand the situation on the ground, to identify partners and to determine the most pressing health needs and how we should work to meet these needs. We now have a targeted approach to providing effective support to the Ministry of Health in addressing this health crisis.”

Working in close conjunction with the Ministry of Health, WHO will increase health workers’ capacity to conduct epidemiological surveillance will be reinforced through training with a particular focus on early warning and response and through integration into the system of active malnutrition surveillance.

Active surveillance of malnutrition will be reinforced. Health staff will be trained in detecting moderate and severe malnutrition according to international standards.

Increased access of malnourished children to health centres for treatment will be addressed. Currently, many clinics require patients to pay, which prevents impoverished children and their parents from seeking care.

WHO will also work closely together with the Ministry of Health to maximize coordination of health-related activities among UN agencies and other humanitarian actors.

A 12 member Emergency Task Force to include a nutritionist, epidemiologist, health systems financing specialist, logistician, project manager and information officer is being assembled for deployment soon.

The WHO component of the Revised Flash Appeal for Niger is part of a wider Revised UN Consolidated Flash Appeal launched on 4 August 2005, which seeks a total of US$ 81 million to assist Niger through the immediate lean agricultural season and to respond to medium term needs up until December 2005.

The Revised UN Consolidated Flash Appeal for Niger includes ACF, Helen Keller International, FAO, OCHA, UNDG, UNDP, UNFPA, UNICEF, WFP, WHO, VSF-B. Projects aim at providing the most affected populations with 73 metric tons of food aid, reinforcing basic primary health care to save lives of moderately and severely malnourished children, preserving livestock and improving food security conditions, strengthening current water sources and sanitations systems to improve hygiene and preventing waterborne diseases, and reinforcing coordination mechanisms as well as information management and advocacy efforts.

- Revised UN Consolidated Flash Appeal for Niger
- WHO’s Action in crises

For more information contact:
Marko Kokic – Information Officer
Health Action in Crises
WHO Geneva